1. Field of the Invention
The present invention relates to a method for measuring at least one glycoprotein selected from alpha-1-acid glycoprotein (AGP) and Mac-2-binding protein (M2BP), a method for examining liver disease using at least one glycoprotein selected from AGP and M2BP, and a glycan-marker glycoprotein with which hepatic cell carcinoma and background liver status such as regarding inflammation-fiber formation can be detected based on glyco-alterations.
2. Description of the Related Art
Liver cancer can be roughly classified into primary liver cancer and metastatic liver cancer developed in the liver. It is said that hepatic cell carcinoma accounts for 90% of primary liver cancer cases.
Hepatic cell carcinoma patients are often infected with hepatitis type C virus or hepatitis type B virus that constitutes the underlying cause of a disease. The disease proceeds from acute viral hepatitis to chronic viral hepatitis, and then to cirrhosis. Long after the development of viral hepatitis, the disease can become cancerous for the first time. In the case of cirrhosis, normal hepatocytes decrease through repetition of inflammation and regeneration, and then the affected liver becomes an organ composed of fibrous tissue. For example, there are said to be 3 million type C hepatitis patients in Japan alone and 10 million or more in China and Africa. Also, in the case of type B and/or type C hepatitis patients, the carcinogenic rate from chronic hepatitis is an annual rate of 0.8% for mild chronic hepatitis (F1), an annual rate of 0.9% for moderate chronic hepatitis (F2), and an annual rate of 3.5% for severe chronic hepatitis (F3). Furthermore, the probability of cirrhosis (F4) becoming cancerous increases to an annual rate of as high as 7% (FIG. 1 and FIG. 2). Also, in the course of liver disease, firstly, functions start to disappear because of chronic hepatitis as the clinical conditions proceed, pathological structure(s) appear because of cirrhosis, and fiber formation of the liver proceeds. In this manner, the tissue image is altered (FIG. 3).
Early detection of cancer is important for cancer treatment. Also, in the case of hepatic cell carcinoma, early detection of cancer significantly influences treatment and postoperative prognosis. The 5-year survival rate after hepatic resection is 80% for stage I cancer and only 38% for stage IV cancer.
As liver cancer markers, α-fetoprotein (AFP) and a protein induced by Vitamin K absence or antagonist-II (PIVKA-II) are currently known (patent documents 1 and 2), but both the specificity and the sensitivity thereof are insufficient. Hence, physical examination for early detection of liver cancer is currently conducted with the use of liver cancer markers and imaging studies such as ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI).
Also, non-patent document 1 describes an attempt to measure fucosylated AGP in serum using AAL lectin so as to detect cirrhosis. However, the technique described in non-patent document 1 is unsatisfactory in view of liver disease detection performance, since the specificity is about 87% and the accuracy is about 77%, although the sensitivity is about 66%, as understood from the results described in Table 2.
Also, non-patent document 2 describes an experiment conducted by measuring asialo AGP in sera of healthy subjects, acute hepatitis patients, chronic hepatitis patients, cirrhosis patients, and hepatic cell carcinoma patients by immunochromatography using RCA lectin, so as to reveal whether each liver disease could be determined to be positive or not. However, the technique described in non-patent document 2 is unsatisfactory in view of liver disease detection performance, since the sensitivity of cirrhosis detection, for example, is about 88%, but the false positive rate for chronic hepatitis patients is 63%, as understood from the results described in Table 2.